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author:("Nguyen, nha")
1.  Design and synthesis of chalcone derivatives as potential non-purine xanthine oxidase inhibitors 
SpringerPlus  2016;5(1):1789.
Background
Based on some previous research, the chalcone derivatives exhibited potent xanthine oxidase inhibitory activity, e.g. sappanchalcone (7), with IC50 value of 3.9 μM, was isolated from Caesalpinia sappan. Therefore, objectives of this research are design and synthesis of 7 and other chalcone derivatives by Claisen–Schmidt condensation and then evaluate their XO inhibitory activity.
Results
Fifteen chalcone derivatives were synthesized by Claisen–Schmidt condensation, and were evaluated for XO inhibitory activity. Nine out of 15 synthetic chalcones showed inhibitory activity (3; 5–8; 10–13). Sappanchalcone derivatives (11) (IC50, 2.5 μM) and a novel chalcone (13) (IC50, 2.4 μM) displayed strong xanthine oxidase inhibitory activity that is comparable to allopurinol (IC50, 2.5 μM). The structure–activity relationship of these chalcone derivatives was also presented.
Conclusions
It is the first research on synthesis sappanchalcone (7) by Claisen–Schmidt condensation. The overall yield of this procedure was 6.6 %, higher than that of reported procedure (4 %). Design, synthesis, and evaluation of chalcone derivatives were carried out. This result suggests that the chalcone derivative can be used as potential non-purine XO inhibitors.Graphical abstractThe chalcone derivatives as potential non-purine xanthine oxidase inhibitors
Electronic supplementary material
The online version of this article (doi:10.1186/s40064-016-3485-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s40064-016-3485-6
PMCID: PMC5063830  PMID: 27795931
Sappanchalcone; Chalcone; Non-purine xanthine oxidase inhibitors
2.  Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata 
JCI Insight  null;1(15):e89790.
BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-γ transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA.
METHODS. We initiated an open-label clinical trial of 12 patients with moderate-to-severe AA, using oral ruxolitinib, 20 mg twice per day, for 3–6 months of treatment followed by 3 months follow-up off drug. The primary endpoint was the proportion of subjects with 50% or greater hair regrowth from baseline to end of treatment.
RESULTS. Nine of twelve patients (75%) demonstrated a remarkable response to treatment, with average hair regrowth of 92% at the end of treatment. Safety parameters remained largely within normal limits, and no serious adverse effects were reported. Gene expression profiling revealed treatment-related downregulation of inflammatory markers, including signatures for CTLs and IFN response genes and upregulation of hair-specific markers.
CONCLUSION. In this pilot study, 9 of 12 patients (75%) treated with ruxolitinib showed significant scalp hair regrowth and improvement of AA. Larger randomized controlled trials are needed to further assess the safety and efficacy of ruxolitinib in the treatment of AA.
TRIAL REGISTRATION. Clinicaltrials.gov NCT01950780.
FUNDING. Locks of Love Foundation, the Alopecia Areata Initiative, NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the Irving Institute for Clinical and Translational Research/Columbia University Medical Center Clinical and Translational Science Award (CUMC CTSA).
Ruxolitinib, a small molecule inhibitor of JAK1 and JAK2, demonstrated efficacy at reversing alopecia areata in a pilot open label clinical trial of twelve patients.
doi:10.1172/jci.insight.89790
PMCID: PMC5033756  PMID: 27699253
3.  Anti-cholinesterases and memory improving effects of Vietnamese Xylia xylocarpa 
Background
Alzheimer’s disease (AD) is the most common cause of dementia among the elderly and is characterized by loss of memory and other cognitive functions. An increase in AChE (a key enzyme in the cholinergic nervous system) levels around β-amyloid plaques and neurofibrillary tangles is a common feature of AD neuropathology. Amnesic effects of scopolamine (acetylcholine receptor antagonist) can be investigated in various behavioral tests such as Morris water maze, object recognition, Y-maze, and passive avoidance. In the scope of this paper, we report the anti-AChE, anti-BChE properties of the isolated compound and the in vivo effects of the methanolic extract of Xylia xylocarpa (MEXX) on scopolamine-induced memory deficit.
Results
In further phytochemistry study, a new hopan-type triterpenoid, (3β)-hopan-3-ol-28,22-olide (1), together with twenty known compounds were isolated (2–21). Compound 1, 2, 4, 5, 7–9, and 11–13 exhibited potent acetylcholinesterase (AChE) inhibitory activity in a concentration-dependent manner with IC50 values ranging from 54.4 to 94.6 μM. Compound 13 was also shown anti-butyrylcholinesterase (BChE) activity with an IC50 value of 42.7 μM. The Morris water Y-maze, Y-maze, and object recognition test were also carried out.
Conclusions
It is noteworthy that MEXX is effective when administered orally to mice, experimental results are consistent with the traditional use of this medicinal plant species.
Electronic supplementary material
The online version of this article (doi:10.1186/s13065-016-0197-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s13065-016-0197-5
PMCID: PMC4973094  PMID: 27493681
Xylia xylocarpa; Hopan-ol-olide; Acetylcholinesterase; Butyrylcholinesterase; Improving memory effects
4.  α-Glucosidase inhibitors from the bark of Mangifera mekongensis 
Background
Mangifera mekongensis (Anacardiaceae) is cultivated for its edible fruit and has been used in traditional Vietnamese medicine for its anti-aging properties and for treating diabetes, vermifuge, and dysentery. As part of a search for biologically active compounds with reduction of the rate of glucose absorption, a screening has been initiated to evaluate natural product extracts for the inhibition of enzyme α-glucosidase. A n-hexane extract of the bark of M. mekongensis showed strong α-glucosidase inhibitory activity with IC50 value of 1.71 µg/mL. Thus, the constituents of this plant were examined.
Results
Two new steroids named mekongsterol A (1) and mekongsterol B (2), were isolated from the n-hexane extract of the bark of M. mekongensis (Anacardiaceae), together with seven known compounds (3–9). Their chemical structures were elucidated on the basis of spectroscopic data. All compounds possessed significant α-glucosidase inhibitory activity in a concentration-dependent manner, except for 3 and 4. Compounds 1, 2, 5–9 showed more potent inhibitory activity, with IC50 values ranging from 1.2 to 112.0 µM, than that of a positive control acarbose (IC50, 214.5 µM).
Conclusions
These results suggested that the traditional use of the bark of M. mekongensis for the treatment of diabetes diseases in Vietnam may be attributable to the α-glucosidase inhibitory activity of its steroid and cycloartane constituents.
Electronic supplementary material
The online version of this article (doi:10.1186/s13065-016-0193-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s13065-016-0193-9
PMCID: PMC4955201  PMID: 27446235
Mangifera mekongensis; Anacardiaceae; α-Glucosidase inhibition; Sterols
5.  Self-powered p-NiO/n-ZnO heterojunction ultraviolet photodetectors fabricated on plastic substrates 
APL materials  2015;3(10):106101.
A self-powered ultraviolet (UV) photodetector (PD) based on p-NiO and n-ZnO was fabricated using low-temperature sputtering technique on indium doped tin oxide (ITO) coated plastic polyethylene terephthalate (PET) substrates. The p-n heterojunction showed very fast temporal photoresponse with excellent quantum efficiency of over 63% under UV illumination at an applied reverse bias of 1.2 V. The engineered ultrathin Ti/Au top metal contacts and UV transparent PET/ITO substrates allowed the PDs to be illuminated through either front or back side. Morphology, structural, chemical and optical properties of sputtered NiO and ZnO films were also investigated.
doi:10.1063/1.4932194
PMCID: PMC4759661  PMID: 26900532
6.  Tyrosinase inhibitory activity of flavonoids from Artocarpus heterophyllous 
Background
Tyrosinase is an oxidoreductase that is very important in medicine and cosmetics because the excessive production of melanin causes hyperpigmentation. The development of novel, effective tyrosinase inhibitors has long been pursued. In preliminary tests, we found that an extract of the wood of Artocarpus heterophyllous (AH) potently inhibited tyrosinase activity.
Results
Two new flavonoids, artocaepin E (1) and artocaepin F (2), were isolated from the wood of AH, together with norartocarpetin (3), artocarpanone (4), liquiritigenin (5), steppogenin (6), and dihydromorin (7). Their structures were elucidated using one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and mass spectrometry. The absolute configuration of 2 was determined from the circular dichroism (CD) spectrum. Artocarpanone (4) had the most potent tyrosinase inhibitory effect, with an IC50 of 2.0 ± 0.1 μM, followed by artocaepin E (1) and steppogenin (6), with IC50 values of 6.7 ± 0.8 and 7.5 ± 0.5 μM, respectively. A kinetic investigation indicated that 1 showed competitive inhibition, with an inhibition constant (Ki) of 6.23 μM.
Conclusions
These results demonstrate that extracts of the wood of AH and its phytochemical constituents are potential sources for skin-whitening agents.Graphical abstractArtocarmin E (1) and artocarmin F (2) were isolated from the wood of Artocarpus heterophyllous. Their structures were elucidated using nuclear magnetic resonance analysis and mass spectrometric methods
Electronic supplementary material
The online version of this article (doi:10.1186/s13065-016-0150-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s13065-016-0150-7
PMCID: PMC4734850  PMID: 26834825
Artocarpus heterophyllous; Flavonoids; Chalcones; Tyrosinase inhibitors
7.  Recovery of Native Renal Function in Patients with Hepatorenal Syndrome Following Combined Liver and Kidney Transplant with Mercaptoacetyltriglycine-3 Renogram: Developing a Methodology 
Many patients with hepatorenal syndrome (HRS) end up receiving a combined liver and kidney transplant (CKLT) with preservation of native kidneys, specially type 1 HRS since is characterizes by a very rapid deterioration of renal function. Eventually, most of the patients regain renal function, but it is unknown if this is due to the transplanted kidney, the recovery of native renal function, or both. The aim of this study is to evaluate if there is recovery of native renal function in patients with HRS following CKLT. 22 patients (16 men; 6 women) with history of HRS and status post CKLT were studied. Mercapto-acetyltriglycine-3 renograms in the anterior and posterior views with the three kidneys in the field of view were simultaneously acquired. The renograms were analyzed by creating regions of interest around the transplanted and native kidneys. Relative contribution to the renal function, clearance, and effective renal plasma flow for the transplanted and native kidneys were obtained. 1/22 (4.5%) patients presented with a very poor functioning transplanted kidney, in 15/22 (68%) cases the combined native renal function was markedly poorer than the transplanted renal function and in 6/22 (27%) native kidneys showed a contribution to the renal function similar to the transplanted kidney. In conclusion, our series show that around 32% of the HRS patients recovered their native renal function after CKLT. Identification of common factors that affect recovery of native renal function may help to avoid unnecessary renal transplants, significantly reducing morbidity and cost, while facilitating a reallocation of scarce donor resources.
doi:10.4103/1450-1147.172140
PMCID: PMC4729014  PMID: 26912978
Combined liver and kidney transplant; Economic and Social Research Institute; kidney transplant; renal insufficiency; renogram
8.  The dark side of ZNF217, a key regulator of tumorigenesis with powerful biomarker value 
Oncotarget  2015;6(39):41566-41581.
The recently described oncogene ZNF217 belongs to a chromosomal region that is frequently amplified in human cancers. Recent findings have revealed that alternative mechanisms such as epigenetic regulation also govern the expression of the encoded ZNF217 protein. Newly discovered molecular functions of ZNF217 indicate that it orchestrates complex intracellular circuits as a new key regulator of tumorigenesis. In this review, we focus on recent research on ZNF217-driven molecular functions in human cancers, revisiting major hallmarks of cancer and highlighting the downstream molecular targets and signaling pathways of ZNF217. We also discuss the exciting translational medicine investigating ZNF217 expression levels as a new powerful biomarker, and ZNF217 as a candidate target for future anti-cancer therapies.
PMCID: PMC4747174  PMID: 26431164
ZNF217; oncogene; biomarker; hallmarks of cancer; carcinogenesis
9.  Exciton-dominated Dielectric Function of Atomically Thin MoS2 Films 
Scientific Reports  2015;5:16996.
We systematically measure the dielectric function of atomically thin MoS2 films with different layer numbers and demonstrate that excitonic effects play a dominant role in the dielectric function when the films are less than 5–7 layers thick. The dielectric function shows an anomalous dependence on the layer number. It decreases with the layer number increasing when the films are less than 5–7 layers thick but turns to increase with the layer number for thicker films. We show that this is because the excitonic effect is very strong in the thin MoS2 films and its contribution to the dielectric function may dominate over the contribution of the band structure. We also extract the value of layer-dependent exciton binding energy and Bohr radius in the films by fitting the experimental results with an intuitive model. The dominance of excitonic effects is in stark contrast with what reported at conventional materials whose dielectric functions are usually dictated by band structures. The knowledge of the dielectric function may enable capabilities to engineer the light-matter interactions of atomically thin MoS2 films for the development of novel photonic devices, such as metamaterials, waveguides, light absorbers, and light emitters.
doi:10.1038/srep16996
PMCID: PMC4657050  PMID: 26598075
10.  Myocardial blood flow measurement with a conventional dual-head SPECT/CT with spatiotemporal iterative reconstructions - a clinical feasibility study 
Cardiac single photon emission computed tomography (SPECT) cameras typically rotate too slowly around a patient to capture changes in the blood pool activity distribution and provide accurate kinetic parameters. A spatiotemporal iterative reconstruction method to overcome these limitations was investigated. Dynamic rest/stress 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) SPECT/CT was performed along with reference standard rest/stress dynamic positron emission tomography (PET/CT) 13N-NH3 in five patients. The SPECT data were reconstructed using conventional and spatiotemporal iterative reconstruction methods. The spatiotemporal reconstruction yielded improved image quality, defined here as a statistically significant (p<0.01) 50% contrast enhancement. We did not observe a statistically significant difference between the correlations of the conventional and spatiotemporal SPECT myocardial uptake K 1 values with PET K 1 values (r=0.25, 0.88, respectively) (p<0.17). These results indicate the clinical feasibility of quantitative, dynamic SPECT/CT using 99mTc-MIBI and warrant further investigation. Spatiotemporal reconstruction clearly provides an advantage over a conventional reconstruction in computing K 1.
PMCID: PMC3867729  PMID: 24380045
Dynamic SPECT; myocardial perfusion imaging; 99mTc-MIBI; SPECT/CT; spatiotemporal reconstruction; uptake rate constant
11.  Combined SPECT and Multidetector CT for Prostate Cancer Evaluations 
111In-capromab pendetide is an imaging probe for noninvasive detection of prostate cancer dissemination, and can be difficult to interpret because of low photon statistics resulting in noisy images with limited anatomical precision. We examined if a 16-slice multidetector computed tomography (MDCT) combined with single photon emission computed tomography (SPECT) could increase the impact on the clinical management and improve confidence in SPECT image interpretations in comparison to a relatively low-mA (limited resolution) CT. 17 scans were reviewed from a SPECT combined with low-mA CT scanner; 21 scans were reviewed from a SPECT combined with 16-slice MDCT scanner. Reports of the clinical interpretations from the imaging studies, additional examinations performed by referring physicians as a follow-up to the imaging results, and long-term clinical and laboratory follow-ups were used to define confidence of the SPECT/CT readings and impact of the readings on the patient management. The impact was defined as: the occurrence of the 111In-capromab pendetide interpretation resulted in additional imaging studies or biopsies. MDCT improved the quality and confidence in the characterization of small lymph nodes with or without uptake of 111In-capromab pendetide. The increased confidence with MDCT in SPECT/CT readings was evident in all cases reviewed in this study, and the impact on the clinical management was higher (8 out of 21) using SPECT/MDCT than the impact using SPECT combined with low-mA CT (2 out of 17). The dual-modality SPECT/CT provides a quantifiable benefit when MDCT is used instead of low-mA CT, particularly for prostate cancer evaluations using 111In-capromab pendetide.
PMCID: PMC3260786  PMID: 22267999
prostate cancer; capromab pendetide; SPECT/CT; MDCT; prostate specific membrane antigen (PSMA)
12.  Actions of a picomolar short-acting S1P1 agonist in S1P1-eGFP knock-in mice 
Nature chemical biology  2011;7(5):254-256.
Sphingosine 1-Phosphate Receptor 1 (S1P1) plays a critical role in lymphocyte recirculation and is a clinical target for treatment of multiple sclerosis. By generating a short-duration S1P1 agonist and mice where fluorescently tagged S1P1 replaces wild-type receptor, we elucidate physiological and agonist-perturbed changes in expression of S1P1 at a subcellular level in vivo. We demonstrate differential downregulation of S1P1 on lymphocytes and endothelia following agonist treatment.
doi:10.1038/nchembio.547
PMCID: PMC3430385  PMID: 21445057
13.  Combined SPECT and multidetector CT for prostate cancer evaluations 
111In-capromab pendetide is an imaging probe for noninvasive detection of prostate cancer dissemination, and can be difficult to interpret because of low photon statistics resulting in noisy images with limited anatomical precision. We examined if a 16-slice multidetector computed tomography (MDCT) combined with single photon emission computed tomography (SPECT) could increase the impact on the clinical management and improve confidence in SPECT image interpretations in comparison to a relatively low-mA (limited resolution) CT. 17 scans were reviewed from a SPECT combined with low-mA CT scanner; 21 scans were reviewed from a SPECT combined with 16-slice MDCT scanner. Reports of the clinical interpretations from the imaging studies, additional examinations performed by referring physicians as a follow-up to the imaging results, and long-term clinical and laboratory follow-ups were used to define confidence of the SPECT/CT readings and impact of the readings on the patient management. The impact was defined as: the occurrence of the 111In-capromab pendetide interpretation resulted in additional imaging studies or biopsies. MDCT improved the quality and confidence in the characterization of small lymph nodes with or without uptake of 111In-capromab pendetide. The increased confidence with MDCT in SPECT/CT readings was evident in all cases reviewed in this study, and the impact on the clinical management was higher (8 out of 21) using SPECT/MDCT than the impact using SPECT combined with low-mA CT (2 out of 17). The dual-modality SPECT/CT provides a quantifiable benefit when MDCT is used instead of low-mA CT, particularly for prostate cancer evaluations using 111In-capromab pendetide.
PMCID: PMC3260786  PMID: 22267999
Prostate cancer; capromab pendetide; SPECT/CT; MDCT; prostate specific membrane antigen (PSMA)
14.  Distinct Activities of the α-Catenin Family, α-Catulin and α-Catenin, on β-Catenin-Mediated Signaling 
Molecular and Cellular Biology  2004;24(6):2410-2422.
α-Catenin, an integral part of cadherin-catenin adhesion complexes, is a major binding partner of β-catenin, a key component of the Wnt pathway, which activates T-cell factor (TCF)/lymphoid enhancer factor (LEF) transcription and is often upregulated in cancers. Recently, we identified an α-catenin-related protein, α-catulin, whose function is poorly understood, as part of a Rho GTPase signaling complex. Here, based on evidence suggesting that α-catulin may associate with a β-catenin fraction, we investigated the role of α-catenin family members in β-catenin-mediated signals. Expression of the full length or a 103-residue region of α-catenin strongly inhibits the induction of the TCF/LEF-responsive TOPFLASH reporter in HEK293T cells expressing activated β-catenin or in cancer cells with constitutively upregulated Wnt signaling, whereas α-catulin expression had no effect. Interestingly, α-catulin expression attenuates the activation of the cyclin D1 promoter, a target of Wnt pathway signals. α-Catulin appears to inhibit Ras-mediated signals to the cyclin D1 promoter, rather than β-catenin signals, and the synergy between Ras and β-catenin required to fully activate this promoter. Data suggesting the involvement of Rho in this response are presented and discussed. These results suggest a novel function for α-catulin and imply that α-catenin and α-catulin have distinct activities that downregulate, respectively, β-catenin and Ras signals converging on the cyclin D1 promoter.
doi:10.1128/MCB.24.6.2410-2422.2004
PMCID: PMC355851  PMID: 14993280
15.  Replacement of Pre-T Cell Receptor Signaling Functions by the CD4 Coreceptor 
An important checkpoint in early thymocyte development ensures that only thymocytes with an in-frame T cell receptor for antigen β (TCR-β) gene rearrangement will continue to mature. Proper assembly of the TCR-β chain into the pre-TCR complex delivers signals through the src-family protein tyrosine kinase p56lck that stimulate thymocyte proliferation and differentiation to the CD4+CD8+ stage. However, the biochemical mechanisms governing p56lck activation remain poorly understood. In more mature thymocytes, p56lck is associated with the cytoplasmic domain of the TCR coreceptors CD4 and CD8, and cross-linking of CD4 leads to p56lck activation. To study the effect of synchronously inducing p56lck activation in immature CD4−CD8− thymocytes, we generated mice expressing a CD4 transgene in Rag2−/− thymocytes. Remarkably, without further experimental manipulation, the CD4 transgene drives maturation of Rag2−/− thymocytes in vivo. We show that this process is dependent upon the ability of the CD4 transgene to bind Lck and on the expression of MHC class II molecules. Together these results indicate that binding of MHC class II molecules to CD4 can deliver a biologically relevant, Lck-dependent activation signal to thymocytes in the absence of the TCR-α or -β chain.
PMCID: PMC2196103  PMID: 8996248

Results 1-15 (15)